dbSNP rs11001560: DKK1:c.406+282T>C (chr10-52315367-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012242.4(DKK1):c.406+282T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 309,032 control chromosomes in the GnomAD database, including 50,044 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 26511 hom., cov: 31)

Exomes 𝑓: 0.54 ( 23533 hom. )

Consequence

DKK1
NM_012242.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.66

Publications

8 publications found

Variant links:

Genes affected

DKK1 (HGNC:2891): (dickkopf WNT signaling pathway inhibitor 1) This gene encodes a member of the dickkopf family of proteins. Members of this family are secreted proteins characterized by two cysteine-rich domains that mediate protein-protein interactions. The encoded protein binds to the LRP6 co-receptor and inhibits beta-catenin-dependent Wnt signaling. This gene plays a role in embryonic development and may be important in bone formation in adults. Elevated expression of this gene has been observed in numerous human cancers and this protein may promote proliferation, invasion and growth in cancer cell lines. [provided by RefSeq, Sep 2017]

DKK1 links:

PRKG1-AS1 (HGNC:45029): (PRKG1 antisense RNA 1)

PRKG1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK1	NM_012242.4 link	c.406+282T>C		intron_variant	Intron 2 of 3	ENST00000373970.4	NP_036374.1	O94907I1W660

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKK1	ENST00000373970.4 link	c.406+282T>C		intron_variant	Intron 2 of 3	1	NM_012242.4	ENSP00000363081.3		O94907

Frequencies

GnomAD3 genomes

AF:

0.582

AC:

88325

AN:

151784

Hom.:

26463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.696

Gnomad AMI

AF:

0.596

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.667

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.489

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.565

Gnomad OTH

AF:

0.593

GnomAD4 exome

AF:

0.537

AC:

84307

AN:

157130

Hom.:

23533

AF XY:

0.539

AC XY:

42959

AN XY:

79662

show subpopulations

African (AFR)

AF:

0.676

AC:

3427

AN:

5070

American (AMR)

AF:

0.470

AC:

2202

AN:

4684

Ashkenazi Jewish (ASJ)

AF:

0.657

AC:

4052

AN:

6168

East Asian (EAS)

AF:

0.316

AC:

4287

AN:

13564

South Asian (SAS)

AF:

0.475

AC:

758

AN:

1596

European-Finnish (FIN)

AF:

0.485

AC:

5890

AN:

12150

Middle Eastern (MID)

AF:

0.714

AC:

611

AN:

856

European-Non Finnish (NFE)

AF:

0.558

AC:

57059

AN:

102288

Other (OTH)

AF:

0.560

AC:

6021

AN:

10754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1776

3552

5329

7105

8881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.582

AC:

88425

AN:

151902

Hom.:

26511

Cov.:

AF XY:

0.576

AC XY:

42726

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.697

AC:

28872

AN:

41422

American (AMR)

AF:

0.507

AC:

7740

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

2312

AN:

3468

East Asian (EAS)

AF:

0.294

AC:

1516

AN:

5148

South Asian (SAS)

AF:

0.512

AC:

2464

AN:

4808

European-Finnish (FIN)

AF:

0.489

AC:

5152

AN:

10534

Middle Eastern (MID)

AF:

0.714

AC:

210

AN:

294

European-Non Finnish (NFE)

AF:

0.565

AC:

38369

AN:

67944

Other (OTH)

AF:

0.593

AC:

1248

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1823

3647

5470

7294

9117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.582

Hom.:

3981

Bravo

AF:

0.588

Asia WGS

AF:

0.449

AC:

1563

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.0

(source)

DANN

Benign

0.28

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over